A Bayesian Insertion/Deletion Algorithm for Distant Protein Motif Searching via Entropy Filtering

2004 ◽  
Vol 99 (466) ◽  
pp. 409-420 ◽  
Author(s):  
Jun Xie ◽  
Ker-Chau Li ◽  
Minou Bina
Keyword(s):  
Protein Motif ◽  
Motif Searching ◽  
Deletion Algorithm

TBC proteins: GAPs for mammalian small GTPase Rab?

2011 ◽  
Vol 31 (3) ◽  
pp. 159-168 ◽  
Author(s):  
Mitsunori Fukuda
Keyword(s):  
Insulin Resistance ◽  
Small Gtpases ◽  
Structure And Function ◽  
Small Gtpase ◽  
Cell Cycle Regulators ◽  
Gtpase Activating Protein ◽  
Domain Family ◽  
Protein Motif ◽  
Conserved Domain ◽  
And Function

The TBC (Tre-2/Bub2/Cdc16) domain was originally identified as a conserved domain among the tre-2 oncogene product and the yeast cell cycle regulators Bub2 and Cdc16, and it is now widely recognized as a conserved protein motif that consists of approx. 200 amino acids in all eukaryotes. Since the TBC domain of yeast Gyps [GAP (GTPase-activating protein) for Ypt proteins] has been shown to function as a GAP domain for small GTPase Ypt/Rab, TBC domain-containing proteins (TBC proteins) in other species are also expected to function as a certain Rab-GAP. More than 40 different TBC proteins are present in humans and mice, and recent accumulating evidence has indicated that certain mammalian TBC proteins actually function as a specific Rab-GAP. Some mammalian TBC proteins {e.g. TBC1D1 [TBC (Tre-2/Bub2/Cdc16) domain family, member 1] and TBC1D4/AS160 (Akt substrate of 160 kDa)} play an important role in homoeostasis in mammals, and defects in them are directly associated with mouse and human diseases (e.g. leanness in mice and insulin resistance in humans). The present study reviews the structure and function of mammalian TBC proteins, especially in relation to Rab small GTPases.

scholarly journals Detection of Cytosolic Shigella flexneri via a C-Terminal Triple-Arginine Motif of GBP1 Inhibits Actin-Based Motility

mBio ◽  
2017 ◽  
Vol 8 (6) ◽  
Author(s):  
Anthony S. Piro ◽  
Dulcemaria Hernandez ◽  
Sarah Luoma ◽  
Eric M. Feeley ◽  
Ryan Finethy ◽  
...  
Keyword(s):  
Host Cell ◽  
Host Defense ◽  
Actin Polymerization ◽  
Bacterial Pathogens ◽  
Shigella Flexneri ◽  
Bacterial Species ◽  
Host Cells ◽  
Gram Negative Bacteria ◽  
Protein Motif ◽  
Gram Negative

ABSTRACT Dynamin-like guanylate binding proteins (GBPs) are gamma interferon (IFN-γ)-inducible host defense proteins that can associate with cytosol-invading bacterial pathogens. Mouse GBPs promote the lytic destruction of targeted bacteria in the host cell cytosol, but the antimicrobial function of human GBPs and the mechanism by which these proteins associate with cytosolic bacteria are poorly understood. Here, we demonstrate that human GBP1 is unique among the seven human GBP paralogs in its ability to associate with at least two cytosolic Gram-negative bacteria, Burkholderia thailandensis and Shigella flexneri. Rough lipopolysaccharide (LPS) mutants of S. flexneri colocalize with GBP1 less frequently than wild-type S. flexneri does, suggesting that host recognition of O antigen promotes GBP1 targeting to Gram-negative bacteria. The targeting of GBP1 to cytosolic bacteria, via a unique triple-arginine motif present in its C terminus, promotes the corecruitment of four additional GBP paralogs (GBP2, GBP3, GBP4, and GBP6). GBP1-decorated Shigella organisms replicate but fail to form actin tails, leading to their intracellular aggregation. Consequentially, the wild type but not the triple-arginine GBP1 mutant restricts S. flexneri cell-to-cell spread. Furthermore, human-adapted S. flexneri, through the action of one its secreted effectors, IpaH9.8, is more resistant to GBP1 targeting than the non-human-adapted bacillus B. thailandensis. These studies reveal that human GBP1 uniquely functions as an intracellular “glue trap,” inhibiting the cytosolic movement of normally actin-propelled Gram-negative bacteria. In response to this powerful human defense program, S. flexneri has evolved an effective counterdefense to restrict GBP1 recruitment. IMPORTANCE Several pathogenic bacterial species evolved to invade, reside in, and replicate inside the cytosol of their host cells. One adaptation common to most cytosolic bacterial pathogens is the ability to coopt the host’s actin polymerization machinery in order to generate force for intracellular movement. This actin-based motility enables Gram-negative bacteria, such as Shigella species, to propel themselves into neighboring cells, thereby spreading from host cell to host cell without exiting the intracellular environment. Here, we show that the human protein GBP1 acts as a cytosolic “glue trap,” capturing cytosolic Gram-negative bacteria through a unique protein motif and preventing disseminated infections in cell culture models. To escape from this GBP1-mediated host defense, Shigella employs a virulence factor that prevents or dislodges the association of GBP1 with cytosolic bacteria. Thus, therapeutic strategies to restore GBP1 binding to Shigella may lead to novel treatment options for shigellosis in the future. Several pathogenic bacterial species evolved to invade, reside in, and replicate inside the cytosol of their host cells. One adaptation common to most cytosolic bacterial pathogens is the ability to coopt the host’s actin polymerization machinery in order to generate force for intracellular movement. This actin-based motility enables Gram-negative bacteria, such as Shigella species, to propel themselves into neighboring cells, thereby spreading from host cell to host cell without exiting the intracellular environment. Here, we show that the human protein GBP1 acts as a cytosolic “glue trap,” capturing cytosolic Gram-negative bacteria through a unique protein motif and preventing disseminated infections in cell culture models. To escape from this GBP1-mediated host defense, Shigella employs a virulence factor that prevents or dislodges the association of GBP1 with cytosolic bacteria. Thus, therapeutic strategies to restore GBP1 binding to Shigella may lead to novel treatment options for shigellosis in the future.

scholarly journals A Common Motif within the Negative Regulatory Regions of Multiple Factors Inhibits Their Transcriptional Synergy

2000 ◽  
Vol 20 (16) ◽  
pp. 6040-6050 ◽  
Author(s):  
Jorge A. Iñiguez-Lluhí ◽  
David Pearce
Keyword(s):  
Binding Sites ◽  
Regulatory Elements ◽  
General Mechanism ◽  
Proper Function ◽  
Protein Motif ◽  
Regulatory Regions ◽  
Response Elements ◽  
Common Motif ◽  
Single Response ◽  
Dna Regulatory Elements

ABSTRACT DNA regulatory elements frequently harbor multiple recognition sites for several transcriptional activators. The response mounted from such compound response elements is often more pronounced than the simple sum of effects observed at single binding sites. The determinants of such transcriptional synergy and its control, however, are poorly understood. Through a genetic approach, we have uncovered a novel protein motif that limits the transcriptional synergy of multiple DNA-binding regulators. Disruption of these conserved synergy control motifs (SC motifs) selectively increases activity at compound, but not single, response elements. Although isolated SC motifs do not regulate transcription when tethered to DNA, their transfer to an activator lacking them is sufficient to impose limits on synergy. Mechanistic analysis of the two SC motifs found in the glucocorticoid receptor N-terminal region reveals that they function irrespective of the arrangement of the receptor binding sites or their distance from the transcription start site. Proper function, however, requires the receptor's ligand-binding domain and an engaged dimer interface. Notably, the motifs are not functional in yeast and do not alter the effect of p160 coactivators, suggesting that they require other nonconserved components to operate. Many activators across multiple classes harbor seemingly unrelated negative regulatory regions. The presence of SC motifs within them, however, suggests a common function and identifies SC motifs as critical elements of a general mechanism to modulate higher-order interactions among transcriptional regulators.

A cooperative fast annealing coevolutionary algorithm for protein motif extraction

2007 ◽  
Vol 52 (3) ◽  
pp. 318-323
Author(s):  
Chao Chen ◽  
YuanXin Tian ◽  
XiaoYong Zou ◽  
PeiXiang Cai ◽  
JinYuan Mo
Keyword(s):  
Protein Motif ◽  
Coevolutionary Algorithm ◽  
Motif Extraction

scholarly journals Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif

PLoS ONE ◽  
2007 ◽  
Vol 2 (7) ◽  
pp. e645 ◽  
Author(s):  
Viviane Villard ◽  
George W. Agak ◽  
Géraldine Frank ◽  
Ali Jafarshad ◽  
Catherine Servis ◽  
...  
Keyword(s):  
Malaria Vaccine ◽  
Coiled Coil ◽  
Rapid Identification ◽  
Protein Motif ◽  
Vaccine Candidates

scholarly journals Molecular Dynamics Study of a Protein Motif that Senses Packing Defects Induced by Membrane Curvature

2013 ◽  
Vol 104 (2) ◽  
pp. 662a ◽  
Author(s):  
Lydie Vamparys ◽  
Stefano Vanni ◽  
Romain Gautier ◽  
Guillaume Drin ◽  
Bruno Antonny ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Membrane Curvature ◽  
Protein Motif ◽  
Packing Defects

scholarly journals Rewiring yeast sugar transporter preference through modifying a conserved protein motif

2013 ◽  
Vol 111 (1) ◽  
pp. 131-136 ◽  
Author(s):  
E. M. Young ◽  
A. Tong ◽  
H. Bui ◽  
C. Spofford ◽  
H. S. Alper
Keyword(s):  
Sugar Transporter ◽  
Protein Motif
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